1. Field of the Invention
The present invention relates to leukotriene analogues, which are stable, biologically active and useful as antiasthmatic or antiallergic agents.
2. Description of the Prior Art
Recent investigations in the lipoxgenase pathway of the arachidonic acid cascade led to the discovery of leukotrienes, a new class of biologically active eicosanoids (c.f. B. Samuelsson, Pure Appl. Chem., 53: 1203 (1981); P. Borgeat et al, J. Med. chem., 24: 121 (19981); and E. J. Corey et al, J. Amer. Chem. Soc., 102: 1436 (1980)).
The first leukotriene formed in this biosynthetic sequence is leukotriene A.sub.4 (LTA.sub.4, formula 1): ##STR3## LTA.sub.4 is a relatively unstable substance with an epoxide unit. This substance serves as a precursor to leukotrienes B.sub.4 (LTB.sub.4) which are potent chemotactic agents, and to a number of "slow reacting substances of anaphylaxis" (SRS-A) which have been implicated in asthma and other hypersensitivity reactions.
Chemical synthesis has already been achieved for most of the natural leukotrienes, and a number of their isomers (c.f. E. J. Corey et al, J. Amer. Chem. Soc., 102: 1436 (1980); J. Rokach et al, Tetrahedron Lett. 22: 979 (1981); and M. Rosenberger et al, J. Amer. Chem. Soc., 102: 5425 (1980)).
A need, however, continues to exist for stable biologically active leukotriene analogues, in view of their potentially highly useful pharmacological properties.